WO2003084978A1 - Steroidal quinols as prodrugs of antioxidants - Google Patents

Steroidal quinols as prodrugs of antioxidants Download PDF

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Publication number
WO2003084978A1
WO2003084978A1 PCT/US2003/009983 US0309983W WO03084978A1 WO 2003084978 A1 WO2003084978 A1 WO 2003084978A1 US 0309983 W US0309983 W US 0309983W WO 03084978 A1 WO03084978 A1 WO 03084978A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydrogen
quinol
group
alkoxyalkyl
alkylamino
Prior art date
Application number
PCT/US2003/009983
Other languages
English (en)
French (fr)
Inventor
Laszlo Prokai
Katalin Prokai
James Simpkins
Original Assignee
University Of Florida
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University Of Florida filed Critical University Of Florida
Priority to EP03721508A priority Critical patent/EP1490392B1/en
Priority to DE60311779T priority patent/DE60311779T2/de
Priority to AU2003224816A priority patent/AU2003224816A1/en
Publication of WO2003084978A1 publication Critical patent/WO2003084978A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane

Definitions

  • estradien compound refers to estrogen; estrogen metabolites; estrogen analogs, antagonists, or modulators; and compounds with attributes that are categorized as similar or analogous to estrogen, estrogen metabolites, or estrogen analogs, antagonists, or modulators.
  • Therapeutic methods according to the present invention include the controlled administration to a patient of an effective amount of at least one or more of the compounds as set forth above to provide antioxidant therapy.
  • Administration to a patient may range from continuous (intravenous drip) to intramuscular, to several oral administrations per day (for example, Q.I.D.) and may include parenteral, including intravenous and intramuscular, oral, topical, subcutaneous, transdermal (which may include a penetration agent), buccal and suppository administration, among other routes of administration.
  • the estrogen-related steroidal quinols of the present invention may be prepared using known reagents and reactions, including for example, oxidation of estradiol or estrone with tallium, trifluoroacetate, lead tetraacetate, para- nitroperoxybenzoic acid, photooxygenation, or the like.
  • known reagents and reactions including for example, oxidation of estradiol or estrone with tallium, trifluoroacetate, lead tetraacetate, para- nitroperoxybenzoic acid, photooxygenation, or the like.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Fats And Perfumes (AREA)
PCT/US2003/009983 2002-04-01 2003-04-01 Steroidal quinols as prodrugs of antioxidants WO2003084978A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP03721508A EP1490392B1 (en) 2002-04-01 2003-04-01 Steroidal quinols as prodrugs of antioxidants
DE60311779T DE60311779T2 (de) 2002-04-01 2003-04-01 Steroidale Chinole als Prodrugs von Antioxidantien
AU2003224816A AU2003224816A1 (en) 2002-04-01 2003-04-01 Steroidal quinols as prodrugs of antioxidants

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US36958902P 2002-04-01 2002-04-01
US60/369,589 2002-04-01

Publications (1)

Publication Number Publication Date
WO2003084978A1 true WO2003084978A1 (en) 2003-10-16

Family

ID=28791966

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/009983 WO2003084978A1 (en) 2002-04-01 2003-04-01 Steroidal quinols as prodrugs of antioxidants

Country Status (8)

Country Link
US (1) US7026306B2 (pt)
EP (1) EP1490392B1 (pt)
AT (1) ATE353907T1 (pt)
AU (1) AU2003224816A1 (pt)
DE (1) DE60311779T2 (pt)
ES (1) ES2279946T3 (pt)
PT (1) PT1490392E (pt)
WO (1) WO2003084978A1 (pt)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004087160A1 (en) * 2003-04-03 2004-10-14 Prana Biotechnology Ltd Treatment of neurological conditions
WO2005027912A1 (en) * 2003-09-17 2005-03-31 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for estrogen replacement therapy
EP1569648A1 (en) * 2002-12-09 2005-09-07 University of Florida Prodrugs for use a ophthalmic agents
US7026306B2 (en) 2002-04-01 2006-04-11 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for antioxidant therapy
US7186707B2 (en) 2002-04-01 2007-03-06 University Of Florida Prodrugs for use as ophthalmic agents
US7534779B2 (en) 2002-04-01 2009-05-19 University Of Florida Quinol compound and pharmaceutical composition

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2287184T3 (es) * 2000-11-03 2007-12-16 Washington University Estructuras aromaticas modificadas con sustituyentes hidroxi-, que tienen actividad citoprotectora.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5108996A (en) * 1989-03-22 1992-04-28 Roussel Uclaf 19-nor-3-keto steroids
US5395831A (en) * 1994-04-08 1995-03-07 American Home Products Corporation Treating cardiac disorders with Δ9(11)-dehydro-8-isoestrone

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US2910486A (en) * 1957-12-20 1959-10-27 Searle & Co 10-hydroxyestra-1, 4-diene-3, 17-dione and acetate
US2950291A (en) * 1958-12-22 1960-08-23 Searle & Co 17-oxygenated estra-1, 3, 5(10)-triene-1, 4-diols, their esters, and a corresponding quinone
US6197833B1 (en) 1995-07-24 2001-03-06 Apollo Biopharmaceutics, Inc. Neuroprotective effects of polycyclic phenolic compounds
US5554601A (en) 1993-11-05 1996-09-10 University Of Florida Methods for neuroprotection
US5859001A (en) 1996-01-11 1999-01-12 University Of Florida Research Foundation, Inc. Neuroprotective effects of polycyclic phenolic compounds
US6319914B1 (en) 1993-11-05 2001-11-20 Apollo Biopharmaceuticals, Inc. Cytoprotective effect of polycyclic phenolic compounds
JPH11513021A (ja) 1995-08-02 1999-11-09 カイロサイエンス・リミテッド キノロン類およびその医療上の使用
US7488723B2 (en) 2001-09-05 2009-02-10 Alcon, Inc. Use of non-feminizing estrogens as treatment for retinal vascular diseases
US20040214806A1 (en) 2002-09-03 2004-10-28 Iok-Hou Pang Use of non-feminizing estrogens as retinoprotective agents for the treatment of glaucoma
WO2003047559A1 (en) 2001-12-05 2003-06-12 Mitokor, Inc. Use of polycyclic phenolic compounds for the treatment of opthalmic diseases
US7026306B2 (en) 2002-04-01 2006-04-11 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for antioxidant therapy

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5108996A (en) * 1989-03-22 1992-04-28 Roussel Uclaf 19-nor-3-keto steroids
US5395831A (en) * 1994-04-08 1995-03-07 American Home Products Corporation Treating cardiac disorders with Δ9(11)-dehydro-8-isoestrone
US5552395A (en) * 1994-04-08 1996-09-03 American Home Products Corporation Δ9(11)-dehydro-8-isoestrone used to treat alzheimer's disease

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GALDECKI ET AL.: "Structure of 2,4-Dibromo-10beta,17beta-dihydroxy-1,4-estradien-3-one", ACTA CRYST., vol. c43, 1987, pages 967 - 968, XP002247819 *
KUPFER ET AL.: "Comparisons of Hydroperoxide Isomerase and Monooxygenase Activities of Cytochrome P450 for Conversions of Allylic Hydroperoxides and Alcohols to Epoxyalcohols and Diols: Probing Substrate Reorientation in the Active Site", BIOCHEMISTRY, vol. 40, 2001, pages 11490 - 11501, XP002247820 *
NUMAZAWA ET AL.: "Oxygenation of 2,4-Dibromoestrogens with Nitric Acid: A New Synthesis of 19-Nor Steroids", CHEM. PHARM. BULL., vol. 37, no. 8, 1989, pages 2058 - 2062, XP001153599 *
OHE ET AL.: "Novel Metabolic Pathway of Estrone and 17beta-Estradiol Catalyzed by Cytochrome P-450", DRUG METABOLISM AND DISPOSITION, vol. 28, no. 2, 2000, pages 110 - 112, XP002247821 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7026306B2 (en) 2002-04-01 2006-04-11 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for antioxidant therapy
US7186707B2 (en) 2002-04-01 2007-03-06 University Of Florida Prodrugs for use as ophthalmic agents
US7300926B2 (en) 2002-04-01 2007-11-27 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for estrogen replacement therapy
US7534779B2 (en) 2002-04-01 2009-05-19 University Of Florida Quinol compound and pharmaceutical composition
US7572781B2 (en) 2002-04-01 2009-08-11 University Of Florida Prodrugs for use as ophthalmic agents
EP1569648A1 (en) * 2002-12-09 2005-09-07 University of Florida Prodrugs for use a ophthalmic agents
EP1569648A4 (en) * 2002-12-09 2006-10-04 Univ Florida PRODUCTS AS OPHTHALMIC AGENTS
WO2004087160A1 (en) * 2003-04-03 2004-10-14 Prana Biotechnology Ltd Treatment of neurological conditions
WO2005027912A1 (en) * 2003-09-17 2005-03-31 University Of Florida Research Foundation, Inc. Steroidal quinols and their use for estrogen replacement therapy

Also Published As

Publication number Publication date
US20030229060A1 (en) 2003-12-11
PT1490392E (pt) 2007-04-30
ATE353907T1 (de) 2007-03-15
EP1490392B1 (en) 2007-02-14
DE60311779D1 (de) 2007-03-29
EP1490392A1 (en) 2004-12-29
ES2279946T3 (es) 2007-09-01
AU2003224816A1 (en) 2003-10-20
DE60311779T2 (de) 2007-11-22
US7026306B2 (en) 2006-04-11

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